细胞代谢和能量稳态的核心之一是维持嘌呤核苷酸及代谢产物在相对恒定水平，该过程也参与了棕/褐色脂肪细胞的活性调控。腺苷酸琥珀酸合成酶样1（Adssl1）是AMP从头合成途径中的关键酶，参与嘌呤核苷酸循环，其在脂肪中的功能未见报道。我们前期发现Adssl1在棕色及褐色化脂肪组织中高表达；敲减/过表达该基因均不影响褐色脂肪细胞分化，但敲减后的差异表达基因谱与冷暴露后小鼠皮下脂肪组织的表达变化较为一致，提示获得了更接近于棕色化脂肪细胞的表型；相应地，Seahorse检测发现敲减组基础和最大耗氧量均显著增加。初步结果还发现敲减组细胞内嘌呤核苷酸池的变化以及Ⅰ型干扰素途径的抑制，我们推测这些变化可能参与了Adssl1对褐色脂肪细胞的功能调控。后续研究拟在细胞及动物水平，借助各种质谱分析及组织特异性基因敲除小鼠，研究Adssl1影响褐色脂肪活性的生物化学和分子生物学环节，以及在机体能量代谢中的作用。

Non-shivering thermogenesis in brown adipose tissue is the main mechanism for thermoregulatory heat production in small mammals and newborns. Mitochondrial uncoupling protein 1 (UCP1) is essential for the thermogenic mechanism and it's a target of the crucial regulatory signals. Its activity is regulated by purine nucleotides (inhibitory) and fatty acids (activating). Thus, maintaining the relative stable levels of purine nucleotides and its metabolites is crucial to cellular metabolism and energy homeostasis, and this process is also involved in the regulation of brown/beige adipocytes. Adenylosuccinate synthase like 1 (Adssl1), involved in the purine nucleotide cycle, is a key enzyme in the AMP de novo synthesis pathway. However, the function of Adssl1 in adipose tissue has not been reported yet. Our previous work showed that Adssl1 is highly expressed in brown and beige adipose tissue; knocking down/overexpression of this gene does not affect the differentiation of beige adipocytes, but the differentially expressed gene profile after knockdown the gene is more consistent with the expressed profile of subcutaneous adipose tissue from cold challenged mice, suggesting a phenotype of browning; accordingly, the Seahorse test revealed a significant increase in the baseline and maximum oxygen consumption of the Adssl1 knockdown adipocytes. Preliminary results also showed the alteration of nucleotide pool and the inhibition of the type 1 interferon pathway in Adssl1 knockdown group. Therefore, we postulated that these changes may be involved in the functional regulation of Adssl1 in brown adipocytes. In the following study, we aim to study the biochemical and molecular mechanisms involved in the regulation of Adssl1 on brown fat activity and the energy metabolism at in vitro and in vivo through mass spectrometry and adipose tissue-specific knockout mice.